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Antimicrobial Agents and Chemotherapy, March 2003, p. 986-990, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.986-990.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

High Variability of Plasma Drug Concentrations in Dual Protease Inhibitor Regimens

Jean-Baptiste Guiard-Schmid,1* Jean-Marie Poirier,2 Jean-Luc Meynard,3 Philippe Bonnard,1 Ayi Hola Gbadoe,1 Corinne Amiel,1 Frédérique Calligaris,3 Bruno Abraham,1 Gilles Pialoux,1 Pierre-Marie Girard,3 Patrice Jaillon,2 and Willy Rozenbaum1

Department of Clinical Infectious and Tropical Diseases, Tenon Hospital,1 Department of Pharmacology, St. Antoine University Medical School,2 Department of Clinical Infectious and Tropical Diseases, St. Antoine Hospital, Paris, France3

Received 13 June 2002/ Returned for modification 29 August 2002/ Accepted 3 December 2002

Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the Cmin (minimum concentration of drug in plasma) values for RTV and the coadministered PI Cmin values. Mean RTV Cmins are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual Cmin variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower Cmin variability than with the other combinations. Significant positive correlations between RTV Cmin and boosted PI Cmin were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance.

* Corresponding author. Mailing address: Department of Clinical Infectious and Tropical Diseases, Tenon Hospital, 4, rue de la Chine, 75970 Paris Cedex 20, France. Phone: 33 1 56 01 74 21. Fax: 33 1 56 01 74 23. E-mail: jean-baptiste.guiard-schmid{at}tnn.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, March 2003, p. 986-990, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.986-990.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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